The major objective of this research proposal is to study radiation-induced thyroid cancer by coordinated clinical and laboratory investigations. The clinical studies are designed to determine the continuing incidence of radiation-induced thyroid cancer and to evaluate methods of diagnosis and medical and surgical approach to treatment. This will be accomplished by continuing the longitudinal study of patients who have been evaluated at Michael Reese Hospital because of a history of childhood head and neck irradiation. Of 5,300 patients who were so treated, 1,900 have been examined and another 1,600 have been contacted. In this population there is a 37% prevalence of nodules and among those who have had surgery 35% have had thyroid cancer. Follow-up will continue to provide an estimate of the incidence of radiation-induced thyroid cancer, now estimated at least 1.5% of the population at risk per year. Follow-up of patients who had nodules will provide an evaluation of the treatment methods which have been used. Together these will provide the information to develop guidelines for the care of persons with a history of irradiation. Similar studies will continue on the other radiation-induced tumors which have been found, including those of salivary, neural, and parathyroid origin. Laboratory studies will focus on the role of serum thyroglobulin in the diagnosis of thyroid tumors. Plasma thyroglobulin is elevated in a majority of patients with thyroid nodules and in 12% of patients with a history of irradiation but who otherwise appear completely normal. An initially elevated thyroglobulin level indicates a higher risk of forming thyroid nodules. While patients are being followed, it will be possible to determine whether changes in serum thyroglobulin also have clinical relevance in an irradiated population. In patients with thyroid cancer sequential thyroglobulin determinations will be obtained to assess how these measurements should be used clinically. Factors influencing the radioimmunoassay determination of thyroglobulin will be studied.